Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients

被引：70

作者：

Capolunghi, Federica ^{[2
]}

Rosado, Maria M. ^{[2
]}

Cascioli, Simona ^{[2
]}

Girolami, Elia ^{[3
]}

Bordasco, Silvia ^{[3
]}

Vivarelli, Marina ^{[4
]}

Ruggiero, Barbara ^{[4
]}

Cortis, Elisabetta ^{[5
]}

Insalaco, Antonella ^{[5
]}

Fanto, Nicola ^{[6
]}

Gallo, Grazia ^{[6
]}

Nucera, Eleonora ^{[1
]}

Loiarro, Maria ^{[7
,8
]}

Sette, Claudio ^{[7
,8
]}

De Santis, Rita ^{[1
]}

Carsetti, Rita ^{[2
]}

Ruggiero, Vito ^{[1
]}

机构：

[1] R&D Sigma Tau Ind Farmaceut Riunite SpA, Dept Immunol, I-00040 Pomezia, RM, Italy

[2] Children Hosp Bambino Gesu, Cytometry & B Cell Dev Unit, Res Ctr, Rome, Italy

[3] Children Hosp Bambino Gesu, Immunohematol Sect, Rome, Italy

[4] Children Hosp Bambino Gesu, Dept Nephrol & Urol, Div Nephrol, Rome, Italy

[5] Children Hosp Bambino Gesu, Dept Paediat Med, Div Rheumatol, Rome, Italy

[6] R&D Sigma Tau Ind Farmaceut Riunite SpA, Dept Chem, I-00040 Pomezia, RM, Italy

[7] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy

[8] IRCCS, Fdn Santa Lucia, Lab Neuroembryol, Rome, Italy

来源：

RHEUMATOLOGY | 2010年 / 49卷 / 12期

关键词：

SLE; Memory B cells; Toll-like receptor 9; ST2825; MyD88; Autoantibodies; Cell signalling; Cytosine-phosphate-guanine; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TOLL-LIKE RECEPTORS; TOLERANCE CHECKPOINTS; MURINE MODEL; MEMORY; ANTIBODIES; DISEASE; DIFFERENTIATION; AUTOREACTIVITY; AUTOIMMUNITY;

D O I：

10.1093/rheumatology/keq226

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Methods. Peripheral blood mononuclear cells from 10 SLE patients in clinical remission and 2 with active SLE were cultured in the presence of CpG with or without ST2825. Phenotypical analysis of CpG-stimulated cells was performed by flow cytometry. Supernatants were collected to measure antibody production by ELISA and to detect autoantibodies by IF. Results. CpG-induced TLR9 stimulation caused autoantibody secretion in patients with active disease and in the majority of patients in clinical remission. Inhibition of MyD88 completely blocked the de novo generation of PCs and the secretion of autoantibodies. Conclusions. Autoreactive B cells persist in SLE patients during disease remission in the circulating B-cell memory pool. TLR9-dependent activation of memory B cells by pathogens could be one of the mechanisms triggering relapses in SLE. Compounds targeting the TLR/MyD88 pathway may be used as novel therapeutic tools to treat acute disease and to prevent relapses in SLE patients.

引用

页码：2281 / 2289

页数：9

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